Optical techniques and microtools for subcellular delivery and sampling

The vast majority of biochemical and histological assays are conducted upon ensembles of tens or hundreds or thousands of cells. However, there is a robust and increasing volume of evidence that small subpopulations of cells play significant roles in the development of many disease states, and particularly in their evolution toward treatment resistance. As such, a novel suite of optical tools has been and is being developed, offering functionality analogous to traditional techniques but furnishing them with single- or even subcellular resolution. These are designed to probe the operations of life at its most fundamental level, providing insights into the complex, crowded, and seemingly chaotic processes underpinning cellular processes and their malfunctions.In this chapter, the development of these tools will be explored from their origins to their current state of the art, alongside their applications in both proof-of-concept and applied clinical roles. The focus will be upon tools and techniques designed and developed to interact directly with the cell membrane, taking in optical lysis, poration, and fusion techniques alongside surface chemistry and thin-film coatings capable of causing structural effects within a target cell's plasma membrane. Notable successes and problems will be critically analyzed, and the prospects for the future will be discussed with reference to emerging technologies and promising research avenues in the field.